13C-enrichment at carbons 8 and 2 of uric acid after 13C-labeled folate dose in man |
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Authors: | Baggott Joseph E Gorman Gregory S Morgan Sarah L Tamura Tsunenobu |
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Institution: | Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA. |
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Abstract: | To evaluate folate-dependent carbon incorporation into the purine ring, we measured (13)C-enrichment independently at C(2) and C(8) of urinary uric acid (the final catabolite of purines) in a healthy male after an independent oral dose of 6RS]-5-(13)C]-formyltetrahydrofolate (6RS]-5-H(13)CO-H(4)folate) or 10-H(13)CO-7,8-dihydrofolate (10-H(13)CO-H(2)folate). The C(2) position was (13)C-enriched more than C(8) after 6RS]-5-H(13)CO-H(4)folate, and C(2) was exclusively enriched after 10-H(13)CO-H(2)folate. The enrichment of C(2) was greater from 6RS]-5-H(13)CO-H(4)folate than 10-H(13)CO-H(2)folate using equimolar bioactive doses. Our data suggest that formyl C of 6RS]-10-H(13)CO-H(4)folate was not equally utilized by glycinamide ribotide transformylase (enriches C(8)) and aminoimidazolecarboxamide ribotide (AICAR) transformylase (enriches C(2)), and the formyl C of 10-H(13)CO-H(2)folate was exclusively used by AICAR transformylase. 10-HCO-H(2)folate may function in vivo as the predominant substrate for AICAR transformylase in humans. |
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Keywords: | Folate Stable isotope Purine biosynthesis Uric acid Human Mass spectrometry AICAR transformylase GAR transformylase Dihydrofolate reductase 10-Formyldihydrofolate |
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